1.6 - Pharmacology of depression (core drugs) Flashcards
What is the role of serotonin in the central nervous system?
Plays a role in regulation of mood, personality and wakefulness
What are the five classes of antidepressants?
- sertraline
- citalopram
- fluoxetine
- venlafaxine
- mirtazapine
What are the three most commonly prescribed selective serotonin reuptake inhibitors (SSRIs)?
- sertraline
- citalopram
- fluoxetine
What is the primary mechanism of action of sertraline?
Inhibition of serotonin reuptake results in serotonin accumulation
What is the drug target of sertraline?
Serotonin transporter
What are the main side effects of sertraline? (4)
- GI effects (nausea, diarrhoea)
- sexual dysfunction
- anxiety
- insomnia
What is some extra information about sertraline?
- mild inhibition of dopamine transporter
- must be gradually decreased on discontinuation
- partial inhibition of CYP2D6 at high doses (150mg)
What is the primary mechanism of action of citalopram?
Inhibition of serotonin reuptake results in serotonin accumulation
What is the drug target of citalopram?
Serotonin transporter
What are the main side effects of citalopram? (5)
- GI effects (nausea, diarrhoea)
- sexual dysfunction
- anxiety
- insomnia
- prolonged QT interval
What is some extra information about citalopram?
- mild antagonist of muscarinic and histamine (H1) receptors
- must be gradually decreased on discontinuation
- metabolised by CYP2C19
What is the primary mechanism of action of fluoxetine?
Inhibition of serotonin reuptake results in serotonin accumulation
What is the drug target of fluoxetine?
Serotonin transporter
What are the main side effects of fluoxetine? (4)
- GI effects (nausea, diarrhoea)
- sexual dysfunction
- anxiety
- insomnia
What is the primary mechanism of action of venlafaxine?
- more potent inhibitor of serotonin reuptake than norepinephrine reuptake
- noradrenaline is involved in regulation of emotion and cognition
SNRI
What are the drug targets of venlafaxine?
- serotonin transporter
- noradrenaline transporter
What are the main side effects of venlafaxine? (5)
- GI effects (nausea, diarrhoea)
- sexual dysfunction
- anxiety
- insomnia
- hypertension (at higher doses)
What is some extra information about venlafaxine?
Must be gradually decreased on discontinuation
What is the primary mechanism of action of mirtazapine?
- antagonises central presynaptic alpha-2-adrenergic receptors
- causes increased release of serotonin and noradrenaline
- antagonises central 5HT2 receptors, leaving 5HT1 receptors unopposed causing anti-depressant effects
What are the drug targets of mirtazapine?
- alpha-2 receptor
- 5HT2 receptor
What are the main side effects of mirtazapine?
- weight gain
- sedation
What is some extra information about mirtazapine?
- low probability of sexual dysfunction
- may exacerbate REM sleep behaviour disorder
What anti-depressant should you avoid if you are already on a drug associated with QT prolongation (like erythromycin)?
- citalopram - severe interaction
- also: increasing age, female sex, cardiac disease and some metabolic disturbances (notably hypokalaemia) predispose to QT prolongation
If we assume that the anti-depressant effects of SSRIs are solely due to their action at the serotonin transporter, how do we explain the plateau in therapeutic effect?
The serotonin reuptake transporters become fully blocked and concentration of serotonin in synapse becomes maxed out
Why do you have to slowly wean off one antidepressant before starting a new one?
Caution is required when switching from one antidepressant to another due to the risk of drug interactions, serotonin syndrome, withdrawal symptoms or relapse
At very high doses, what effect can mirtazapine have?
Anti-emetic effect (acts on 5HT3 receptor)
Describe how changing the dose of mirtazapine can change the response produced.
- at low doses, mirtazapine preferentially blocks the histamine receptor since at lower plasma concentrations it has higher affinity to H1 than serotonergic receptors
- consequently, there is increased duration of sleep at low plasma concentrations and increased sedation at low doses of mirtazapine
- at higher doses, the antihistamine activity is offset by increasing noradrenergic transmission, which reduces its sedating effect
- at very high doses it acts on 5HT3 to have an anti-emetic effect
In order of highest to lowest affinity: H1 (sedation), alpha-2 (antidepressant), 5HT2 (antidepressant), 5HT3 (anti-emetic)
What additional side effect is there with venlafaxine that SSRIs do not have?
Venlafaxine is an SNRI so it has the same side effects as SSRIs but with the addition of hypertension (more adrenaline therefore more vasoconstriction –> high BP)
